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At least 667 records · Page 37Linked to original sources
PubMed2001

The determination of draining lymph node cell cytokine mRNA levels in BALB/c mice following dermal sodium lauryl sulfate, dinitrofluorobenzene, and toluene diisocyanate exposure.

Differential modulation has been demonstrated in interleukin-4 (IL-4), IL-10, and interferon gamma (IFN-gamma) mRNA and protein secretion patterns of cells isolated from the draining lymph nodes of mice following exposure to T cell and respiratory sensitizers. Using a multiprobe ribonuclease protection assay, the following investigation examined the mRNA expression patterns of multiple cytokines associated with respiratory sensitization for modulation following exposure to chemicals known primarily to induce irritation (sodium lauryl sulfate), respiratory sensitization (toluene diisocyanate), or T cell-mediated hypersensitivity (dinitrofluorobenzene) responses. On days 0 and +5 female BALB/c mice were exposed to either test article or vehicle on the shaven dorsal lumbar region; on days +10 through +12 the mice received test article on the dorsal aspect of each ear. On day +13 animals were euthanized, draining lymph nodes were excised, and mRNA was isolated immediately or following 24 or 48 h of culture in the presence or absence of concanavalin (Con) A. Differential expression of cytokine mRNA was most notable following 24 h incubation with Con A. Modulation of IL-4, -10, and IFN-gamma following chemical exposure was consistent with previous studies. In addition, IL-9, -13, and -15 were significantly elevated only following toluene diisocyanate exposure. Further investigations of these cytokines may provide additional insight into the mechanisms of chemically induced respiratory sensitization and provide endpoints for the detection of a chemical's ability to elicit IgE-mediated hypersensitivity responses.

Administration, Topical↗
PubMed2001

Chemical sensitivity and chronic fatigue in Gulf War veterans: a brief report.

The foci of this brief report are to (1) describe the prevalence of chemical sensitivity (CS) and chronic fatigue (CF) symptomatology and of presumptive multiple CS and CF syndrome diagnoses, and (2) explore the potential overlap between one purported case definition (i.e., chronic multi-symptom illness) and these unexplained symptom syndromes in a well-characterized group of Gulf War veterans. The number of subjects with CS and CF symptomatology and presumptive multiple CS and CF syndrome diagnoses was higher in the Gulf War-deployed group compared with a group deployed to Germany during the Gulf War. However, the percent differences were not significant when comparing the presumptive diagnoses of multiple CS and CF syndrome. The characteristic differences between the groups and the overlap with chronic multi-symptom illness are also discussed.

Adult↗
PubMed1985

Selection between multiple periodic regimes in a biochemical system: complex dynamic behaviour resolved by use of one-dimensional maps.

We analyse a model biochemical system in which two autocatalytic enzyme reactions are coupled in series, in conditions where multiple stable periodic regimes coexist for the same set of parameter values. We determine how the periodic regimes are reached from different initial conditions. The structure of the attraction basins is generally simple in the case of two coexisting limit cycles (birhythmicity). This structure and the associated behaviour may, however, become highly complex. In particular, the system exhibits enhanced sensitivity to initial conditions when the boundaries of the attraction basins are fractal. In the latter case, it becomes difficult to predict the evolution towards either one of two limit cycles, a phenomenon known as final state sensitivity. We show how these complex phenomena can be explained in a unified and simple manner by means of one-dimensional return maps derived from the time evolution of the model and from fifth degree polynomial equations. We suggest experimental tests of the sensitivity to initial conditions in chemical systems presenting birhythmicity. The physiological significance of the results is discussed with respect to the sensitivity of regulatory systems admitting multiple stable biological rhythms.

Allosteric Regulation↗
PubMed2004

Multiple-spin analysis of chemical-shift-selective (13C, 13C) transfer in uniformly labeled biomolecules.

Chemical-shift-selective (13C, 13C) polarization transfer is analyzed in uniformly labeled biomolecules. It is shown that the spin system dynamics remain sensitive to the distance of interest and can be well reproduced within a quantum-mechanical multiple-spin analysis. These results lead to a general approach on how to describe chemical-shift-selective transfer in uniformly labeled systems. As demonstrated in the case of ubiquitin, this methodology can be used to detect long-range distance constraints in uniformly labeled proteins.

Biopolymers↗
PubMedDate not supplied

A case of multiple sensitization to three halogeno-substituted mono-nitrobenzenes.

A case of occupational contact dermatitis in a female chemical pharmaceutical laboratory researcher is described. The allergological investigation revealed a state of sensitization to three mono-nitrobenzenes with halogen substitutions in the nucleus or a side chain. Problems related to sensitization to these substances and to possible cross-allergy with DNCB are discussed.

Adult↗
PubMed2004

Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoring.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly caused by 21-hydroxylase deficit (21-OHD). Deletions or mutations of the CYP21 gene induce the impairment of glucocorticoid and mineralcorticoid synthesis. 17-Hydroxyprogesterone (17-OHP) is the hormonal marker in patients, but not in the heterozygous subjects. Excess 17-OHP is hydroxylated into 21-deoxycortisol (21-DF), and therefore 21-DF can be used as a specific marker for diagnosis of heterozygous individuals. We report an analytical method for analysis of 21-DF in blood samples using electrospray (ESI) and atmospheric pressure chemical ionization (APCI), showing that ESI is very sensitive for the analysis of this marker molecule. The multiple reaction monitoring (MRM) approach was used to increase the specificity and the sensitivity of the method.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Experimental study on skin sensitization potencies and cross-reactivities of hair-dye-related chemicals in guinea pigs.

In screening patch testing of hairdressers with occupational contact dermatitis, multiple positive reactions to hair dye-related chemicals, such as p-phenylenediamine (PPD), p-toluenediamine x 2HCl (PTD) and p-aminophenol (PAP), a fabric dye p-aminoazobenzene (PAB), and a tar dye Sudan III, were frequently encountered. To investigate individual skin sensitization potency and the cross-reactivities among above chemicals, a guinea pig maximization test with the above 5 chemicals was performed. In each group, 6 animals were induced with one of the chemicals at 0.1% concentration by intradermal injection and at 1.0% by topical application. The animals were challenged with all 5 chemicals in concentrations of dilution by 10 from 0.1% to 0.001%. Under the conditions of 0.1% challenges, similar sensitization potencies were observed in PPD (6/6), PTD (6/6), PAP (5/6) and PAB (6/6) groups, but no positive reactions were elicited in the Sudan III group. The cross-reactivities to PPD were confirmed in the animals challenged with PTD (6/6), PAP (6/6), PAB (6/6) and Sudan III (3/6). In the PTD-induced group, positive responses to cross-challenges were elicited by PPD (5/6), PAP (3/6), PAB (5/6) and Sudan III (1/6). The cross-reactivities to PAP were observed only with PPD (2/5) and PAB (5/5). PAB-induced animals responded only to PPD (1/6). The results indicate that all these chemicals except Sudan III are strong sensitizers. Their cross-reactivities are different in sensitized conditions, respectively. The cross-reactivities to PPD were higher than those to PTD, PAP and PAB.

Aminophenols↗
PubMed1997

Quantification of heterocyclic amine carcinogens in cooked meats using isotope dilution liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry.

Heterocyclic aromatic amines (HAAs) are formed in cooked meats through pyrolysis reactions of different amino acids in the presence or absence of creatine/creatinine and sugars. HAAs are mutagens, colon/mammary gland carcinogens in rodents, and are suspected in the etiology of human cancers. In this study, cooked meats containing incurred HAAs as well as control (microwave) meat, were spiked with four labeled HAA internal standards (MeIQx, IQ, AAC and PhIP) and extracted using a liquid/liquid cleanup procedure. Isotope dilution measurements were made using on-line liquid chromatography atmosphere pressure chemical ionization tandem mass spectrometry with multiple reaction monitoring to provide the sensitivity and specificity needed for trace analysis in these complex matrices. The procedure was validated using control meat spiked with the four native HAAs at 0-50 ppb. The levels of HAAs found in cooked meats ranged from non-detectable (limit of detection 0.1-1.0 ppb) in microwave-cooked hamburger to 226 ppb PhIP and 104 ppb AAC in well-done grilled chicken. This methodology has the potential to provide accurate data on the consumption of HAAs in the diet for use in human cancer risk assessment.

Amines↗
PubMed1998

Chinese hamster cells meet DNA repair: an entirely acceptable affair.

This personal account relates the advent of mutant isolation and other developments in somatic cell genetics that were critical steps toward isolating DNA repair mutants in mammalian cells. The isolation of auxotrophic and temperature-sensitive mutants in genetically stable Chinese hamster cell during the late 1960s and early 1970s provided a conceptual framework in which to later isolate mutations conferring hypersensitivity to ultraviolet radiation, ionizing radiation, and various chemical mutagens. Complementation group analysis of ultraviolet-sensitive mutants helped identify multiple genes that overlapped with the groups of cancer-prone xeroderma pigmentosum, as well as Cockayne syndrome. The first mammalian cell mutants defective in strand-break repair were also discovered. Subsequent cloning of human genes that corrected CHO-cell mutations in nucleotide-excision repair groups 1-6 later led to identifying the key enzymes in the incision steps of this pathway, as well as the CSB protein, which is involved in coupling excision repair and transcription.

Animals↗
PubMed1992

Isolation and characterization of additional genes influencing resistance to various mutagens in the yeast Saccharomyces cerevisiae.

Screening of a multi-copy vector-based yeast genomic library in haploid cells of wild-type Saccharomyces cerevisiae yielded transformants hyper-resistant to various chemical mutagens. Genetical analysis of the yeast insert DNAs revealed three genes SNG1, SNQ2, and SNQ3 that confer the phenotype hyper-resistance to MNNG, to 4-NQO and triaziquone, and to mutagens 4-NQO, MNNG, and triaziquone, respectively. Integration of the gene disruption-constructs into the haploid yeast genome yielded viable null-mutants with a mutagen-sensitive phenotype. Thus, copy number of these non-essential yeast genes determines the relative resistance to certain chemical mutagens, with zero copies yielding a phenotype of mutagen sensitivity and multiple copies one of mutagen hyper-resistance, respectively.

4-Nitroquinoline-1-oxide↗
PubMed1999

Interaction of HLA phenotype and exposure intensity in sensitization to complex platinum salts.

The development of sensitization to inhaled allergens is determined by the interaction of multiple genetic and environmental influences. Occupational sensitization to low-molecular-weight chemicals allows a specific immunological response to an inhaled hapten to be studied in a well-defined population with characterized exposure. We investigated the workforce of a large platinum refinery exposed to ammonium hexachloroplatinate (ACP) to test the hypothesis that the development of IgE-associated sensitization to ACP was influenced by human leukocyte-associated antigen (HLA) phenotype, especially in those with lower ACP exposure. We performed HLA typing in 44 cases with a positive skin prick test to ACP, and 57 nonsensitized referents matched on age, race, duration of employment, and category of ACP exposure. An HLA-DR3 phenotype was more common among cases (odds ratio [OR] 2.3), and more so in those with low (OR infinite) than with high exposure (OR 1.6); HLA-DR6 was less common among the cases (OR 0.4), an association also stronger in the low-exposure group (OR 0.1 versus 0.5). These results provide evidence that HLA phenotype is a significant determinant of sensitization to complex platinum salts and for the first time show that the strength of this association varies with intensity of exposure to the sensitizing agent. They imply that as exposure-control measures are taken to prevent occupational sensitization and, by analogy, sensitization to allergens outside the workplace, disease incidence will increasingly be determined by genetic susceptibility.

Adult↗
PubMed2004

Separation and identification of 20 chemical constituents in the traditional Chinese medicinal preparation Shenbao tablet by LC-ESI-MS3.

A sensitive and specific high-performance liquid chromatography (HPLC)-electrospray ionization multiple-stage mass spectrometry for the simultaneous separation and identification of 20 chemical constituents in the traditional Chinese medicinal preparation of the Shenbao tablet is established. The samples are separated with an Alltima C(18) column (250 x 4.6 mm, 5 microm) by linear gradient elution using water-acetic acid (A; 100:0.5, v/v) and acetonitrile (B; 0 min, 76:24; 15 min, 70:30; 40 min, 53:47; 50 min, 30:70; and maintain 10 min) as the mobile phase at a flow rate of 1.0 mL/min. The ion trap mass spectrometer is coupled to the HPLC system. Satisfactory results are obtained within 60 min for the simultaneous separation and identification of the 20 constituents. This is the first report on the analysis of main chemical constituents in the Shenbao tablet.

Chromatography, High Pressure Liquid↗
PubMed1989

Association of sperm measures with reproductive outcome: National Toxicology Program studies in mice.

In reproductive assessment by continuous breeding (RACB) studies, a crossover mating trial was conducted if an adverse effect on fertility was detectable over an 18-week cohabitation period during which Swiss (CD-1) mice were continuously treated. Results of 25 RACB crossover mating studies conducted to determine the affected sex were compared with results of sperm morphology and vaginal cytology examinations (SMVCE) performed at the conclusion of each mating trial. SMVCE endpoints included epididymal sperm concentration, motility, and morphology, vaginal cytology, and male reproductive organ weights. In most studies, multiple SMVCE endpoints were adversely affected. With this group of chemicals, epididymis weight was sensitive and specific to male reproductive toxicants and nontoxicants, respectively. Sperm motility and testis weight were also highly sensitive to male reproductive toxicants. The above endpoints demonstrated the greatest statistical significance relative to other SMVCE parameters, and were highly associated with fertility measurements from breeding experiments. These characteristics suggest that some SMVCE endpoints are more useful for screening chemicals for potential male reproductive toxicity than others. Caution must be exercised, however, because the compounds used in these studies are not representative of all classes of chemicals, and chemicals not tested here may produce adverse reproductive effects by different mechanisms of action. The dose-response effects of two glycol ethers evaluated in RACB, ethylene glycol monomethyl ether and ethylene glycol monoethyl ether, on reproductive outcome and SMVCE endpoints were examined in detail. Both caused adverse effects on testis weight and sperm head morphology, and these changes were associated with adverse effects on reproductive outcome. Until we have more experience with SMVCE and other screens, multiple endpoints should continue to be used for screening for reproductive toxicants.

Animals↗
PubMed1992

The sensitive determination of abanoquil in blood by high-performance liquid chromatography/atmospheric pressure ionization mass spectrometry.

A method is described for the determination of abanoquil in human blood. The method is based on high-performance liquid chromatography (HPLC)/atmospheric pressure positive ion chemical ionization mass spectrometry, using (2H3)abanoquil as internal standard. Multiple reaction monitoring is employed for selectivity and sensitivity, which enables quantification over the range 10-500 pg ml-1 with acceptable precision and accuracy. This assay methodology illustrates the versatility of atmospheric pressure ionization/tandem mass spectrometry, in conjunction with HPLC, for the separation and quantification of drugs in the subnanogram per millilitre range.

Adrenergic alpha-Antagonists↗
PubMed1990

Multiple endpoints for somatic mutations in humans provide complementary views for biodosimetry, genotoxicity and health risks.

While monitoring people with multi-endpoint analysis is only just beginning, the indications of complementarity of these assays are already evident. Since two different tissue types are analyzed, effects of uneven exposure or tissue-specific sensitivities or development kinetics and persistence of each cell type can be addressed. The differing analytical techniques in determining variant cells lead to particular advantages for each assay procedure. The GPA assay can be performed rather quickly on small blood volumes (as little as 0.1 ml). A similar potential exists for the Hb assay, although sophisticated instrumentation development is still required to make this assay easily performable. Both the HPRT and HLA assays require long term tissue growth and many-fold larger (10-30 ml) blood samples. However, both the HPRT and HLA assays have the advantage that they select variant cells that contain nuclei, so that detailed characterization of their mutagenesis is possible using Southern blots, hybridization analysis, and gene sequencing. Since erythrocytes have no nucleic acids, so these effects cannot be measured using the GPA or Hb assay. Other differences between the assays are the target size, chromosomal location, and control signals. Each gene locus is on a different chromosome, with GPA, HLA and Hb genes on autosomes and HPRT on the X chromosome. The target size for GPA and HPRT are about 40kb, whereas HLA A locus is 5kb and the Hb target is one base. These differences should result in much different sensitivity to different mutagenic phenomena, such as radiation effects or different chemical effects. The multiple differences between assays that are designed to detect similar kinds of events occurring in vivo in humans leads us to conclude that all these assays could well be performed on the same blood samples, and the information gained would be much more than the separate assays could yield. Biodosimetry and estimation of cancer initiation could become realistic goals instead of simply significant desires.

Aging↗
PubMed2002

Effects of neural drives on breathing in the awake state in humans.

We have developed a mathematical model of the regulation of ventilation that successfully simulates breathing in the awake as well as in sleeping states. In previous models, which were used to simulate Cheyne-Stokes breathing and respiration during sleep, the controller was only responsive to chemical stimuli, and allowed no ventilation at sub-normal carbon dioxide levels. The current model includes several new features. The chemical controller responds continuously to changes in P(CO(2)) with a lower sensitivity during hypocapnia than in the hypercapnic ranges. Hypoxia interacts multiplicatively with P(CO(2)) over the entire range of activity. The controller in the current model, besides the chemical drive, includes also a neural component. This neural drive increases and decreases as the level of alertness changes, and adds or subtracts from ventilation levels demanded by the chemical controller. The model also includes the effects of post-stimulus potentiation (PSP) and hypoxic ventilatory depression (HVD). While PSP eliminates apneas after a disturbance and also dampens the subsequent dynamics of the respiration, it is not a major factor in the damping of the response. Another finding is that HVD is destabilizing. The model is the first to reproduce results reported in conscious humans after hyperventilation and after acute and longer-term hypoxia. It also reproduces the effects of NREM sleep.

Arousal↗
PubMed1987

Effects of mycotoxins in cultured kidney cells: cytotoxicity of aflatoxin B1 in Madin-Darby and primary fetal bovine kidney cells.

The cytotoxicity of aflatoxin B1, a fungal metabolite and an important food contaminant, was evaluated in an established cell line, Madin-Darby bovine kidney (MDBK) cells, and in primary fetal bovine kidney (PFBK) cells. Cells were grown in monolayers and treated with media containing AFB1 for 24 hr. Both culture systems were sensitive to the chemical; the PFBK cultures were approximately four times more susceptible to the cytotoxic effect. Cell multiplication decreased in both systems in long-term cultures. Adherence of MDBK cells was only slightly reduced at the toxic concentrations of the chemical. Electron microscopy revealed condensation of chromatin, separation of nuclei from the cytoplasm, cytoplasmic vacuolization, and loss of surface microvilli. Results indicated differential sensitivity of the two culture systems.

Aflatoxin B1↗
PubMedDate not supplied

The covalent attachment of multiple fluorophores to DNA containing phosphorothioate diesters results in highly sensitive detection of single-stranded DNA.

DNA fragments containing multiple internucleotidic phosphorothioate diesters, prepared by either chemical or enzymatic syntheses, are amenable to labeling with the fluorophore monobromobimane. With the incorporation of phosphorothioate diesters at each internucleotidic site, multiple fluorophores, ideally one for each nucleotide residue, can be covalently attached to the DNA fragment. The presence of multiple labels can be expected to interfere with analysis techniques, such as polyacrylamide gel electrophoresis. To avoid such problems, the fluorophores are introduced in a "postassay" fashion, that is, while the fragments are still embedded within the gel matrix. The detection limit (to the naked eye) for multiply labeled single-stranded DNA containing hundreds of base residues is in the low femtomole range. DNA containing greater than 1000 base residues can be visualized in some cases in the subfemtomole range without the use of sophisticated electronic instrumentation.

Bridged Bicyclo Compounds↗